Entrectinib a Plausible Inhibitor for Osteopontin (SPP1) in Cervical Cancer-Integrated Bioinformatic Approach.

Autor: Poleboyina PK; Department of Genetics & Biotechnology, University College of Science, Osmania University, -500007, Hyderabad, Telangana, India., Alagumuthu M; Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, -632014, Vellore, India., Pasha A; Department of Genetics & Biotechnology, University College of Science, Osmania University, -500007, Hyderabad, Telangana, India., Ravinder D; Department of Genetics & Biotechnology, University College of Science, Osmania University, -500007, Hyderabad, Telangana, India., Pasumarthi D; Department of Genetics & Biotechnology, University College of Science, Osmania University, -500007, Hyderabad, Telangana, India., Pawar SC; Department of Genetics & Biotechnology, University College of Science, Osmania University, -500007, Hyderabad, Telangana, India. dr.smitapawar@osmania.ac.in.
Jazyk: angličtina
Zdroj: Applied biochemistry and biotechnology [Appl Biochem Biotechnol] 2023 Dec; Vol. 195 (12), pp. 7766-7795. Date of Electronic Publication: 2023 Apr 22.
DOI: 10.1007/s12010-023-04541-7
Abstrakt: Cervical cancer is one of the major causes of death in women, especially in developing countries bearing more than a quarter of the global burden. Secreted phosphoprotein-1, also known as OPN (osteopontin), is an integrin-binding glycophosphoprotein that is overexpressed in a variety of tumors. OPN is a chemokine-like calcified ECM-associated protein that plays a crucial role in evaluating the metastatic potential of various cancers. However, the role of SPP1 in the tumor microenvironment and associated signaling pathways in CC is still unclear. In our study, three CC microarray datasets (GSE9750, GSE46857, and GSE67522) were obtained from the GEO database to identify the differentially expressed genes. Enrichment analysis was carried out by Enrichr and ShinyGO and the PPI interaction network was created by using String and Cytoscape. GEPIA datasets were used to validate the top 10 hub genes, and virtual screening, docking, and dynamic simulation studies were used to identify a suitable inhibitor against the OPN protein using MVD, PyRx, and GROMACS respectively. Our results show that a total of 11 DEGs were common for three datasets and gene ontology pathway enrichment analysis revealed that 2 biological processes i.e. programmed cell death and animal organ development commonly affected mechanisms in all three datasets. Docking and dynamic studies revealed that Entrectinib showed excellent binding affinity against OPN protein. Based on the results, we conclude that OPN is one of the most upregulated genes in cervical cancer and Entrectinib emerges to be a promising potential OPN inhibitor to curtail cervical cancer progression. Schematic representation: The schematic representation of methodology steps is illustrated in the graphical abstract. Schematic representation of methodology.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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